This document discusses the management of sepsis in patients with cirrhosis. It states that early administration of antibiotics, fluids, vasopressors, and source control are key to managing sepsis, similar to patients without cirrhosis. However, patients with cirrhosis can have altered hemodynamics like elevated cardiac index and lower blood pressure. Serial lactate levels and markers like skin mottling score may help guide resuscitation in these patients. Albumin is preferable to crystalloids for fluid resuscitation. Norepinephrine is the first-line vasopressor. Steroids may be considered for adrenal insufficiency. Timely, appropriate antibiotics and consideration of antifungals for non-responders

1. MANAGEMENT OF SEPSIS IN
CIRRHOSIS
DR MANOJ RAUT
ASSO CONSULTANT
TRANSPLANT ANAESTHESIA AND CRITICAL CARE
SAHYADRI HOSPITAL ,PUNE

2. WHAT IS SEPSIS
• Life-threatening organ dysfunction caused by
a dysregulated host response to infection.
• Organ dysfunction is defined as an increase in
the Sequential Organ Failure Assessment
(SOFA) score of ≥2 points
• septic shock is identified by the requirement
of vasopressors to maintain a mean arterial
pressure (MAP) of ≥65 mm Hg and a serum
lactate level >2 mmol/L.(1)

5. SIMILARITY IN SIRS AND CIRRHOSIS

6. MANAGEMENT OF SEPSIS

7. Initial Management of Patients With
Cirrhosis and Sepsis
• Similar to patients without cirrhosis, early
administration of antibiotic, fluids,
vasopressors, and infectious source control
are the foundation of sepsis management.

9. HEMODYNAMIC MONITORING
• Vascular hyporeactivity and hyperdynamic
circulation, features of advanced cirrhosis, result
in elevated cardiac index, low systemic vascular
resistance, lower MAP, and higher central venous
oxygen saturation.
• In patients with cirrhosis, central venous
pressure (CVP) may reflect increased intra-
abdominal pressure, and static measurements
alone may be misleading for assessment of
volume status.

10. • In patients without ascites, respiratory variation of the
inferior vena cava (IVC) is considered the most accurate
way of measuring fluid responsiveness.
• Variations of >12%-18% in patients on mechanical
ventilation and >40% variability in patients breathing
spontaneously, and an increase in left ventricular
outflow tract velocity time integral >12% during
passive leg raising, separate fluid responders from
nonresponders
• echocardiogram parameters should be ideally assessed
postparacentesis for more-reliable results.

11. MARKERS
• Serum lactate has been routinely used as an
indirect marker of tissue hypoxia in sepsis and is
currently part of the definition of septic shock.
• The hepatic metabolism of lactate is often
impaired in patients with cirrhosis, and serum
lactate levels should be interpreted with caution
in this population
• Serial lactate measurements are likely more
informative and the trend may correlate better
with survival.

12. • Activated protein C has been shown in vitro to
induce protective (anti-inflammatory and
antiapoptotic) genes in endothelial cells.
• non-survivors of septic illnesses have
persistently reduced serum protein C below a
critical level of approximately 60% of
normal,and reconstitution of activated protein
C can improve survival in patients with severe
sepsis.

13. • Additional markers of tissue hypoxia, including
skin mottling score (score ≥2) and tissue
oxygenation saturation (knee StO2) assessed
by laser Doppler, have been recently proposed
in patients with cirrhosis with septic shock and
are associated with poor survival.

14. MONITORING
• The consensus recommendations include the
placement of an arterial line and central venous
access in patients with circulatory shock, and use
of pulmonary artery catheter (PAC) or
echocardiography for monitoring during fluid
resuscitation.
• urine output is used in the initial assessment of
volume status, but it is important to recognize
that oliguria may be the sole indicator of renal
dysfunction in patients with cirrhosis

15. FLUID RESUSCITATION
• Fluid administration represents a key step in management
of sepsis, aiming at prevention of tissue hypoxia and
preservation of organ function.
• Though individual studies have not demonstrated a benefit
of albumin over normal saline,recent meta-analyses
demonstrated lower mortality with albumin compared to
crystalloids or starches in adult patients with sepsis and a
significant reduction in 90-day mortality with albumin
resuscitation in patients with septic shock when compared
to crystalloids.
• Hydroxyethyl starch has been associated with an increased
rate of renal replacement therapy (RRT) when used in
patients with sepsis its use in cirrhosis is not recommended
because of increased risk of nephrotoxicity

16. • Intravenous albumin infusion has been demonstrated
in several studies to reduce mortality in spontaneous
bacterial peritonitis and hepatorenal syndrome and to
improve outcomes following large-volume paracentesis
• it has been suggested that albumin administration be
incorporated in patients with cirrhosis with suspected
infection, with a target of 50-100 g of albumin/day. It is
important to emphasize, however, that adequate
volume resuscitation is imperative in the management
of septic shock independent of the fluid chosen.

17. Vasopressors
• Norepinephrine is considered as a first-line agent for
sepsis and is associated with fewer adverse events
compared to dopamine, which is no longer
recommended
• Norepinephrine’s vasoconstrictor effect allows for
increase in venous return and, consequently, improves
cardiac preload
• Epinephrine acts similarly to norepinephrine, with the
main limitation being its potential to cause
dysrhythmias, myocardial ischemia, pulmonary
hypertension, lactic acidosis, and hyperglycemia

18. • The hyperdynamic circulatory state present in
both septic shock and cirrhosis is associated
with a deficiency of endogenous
vasopressin.Although the SSC does not
recommend vasopressin as monotherapy or
first line for management of septic shock

19. Steroids
• Adrenal insufficiency is common in patients with
cirrhosis presenting with sepsis and septic shock,
although it can also be present in patients with
stable or decompensated cirrhosis.
• Corticosteroids are commonly used in patients
with septic shock, particularly those with
unsatisfactory response to vasopressors
• Recent study demonstrated that combination
hydrocortisone plus fludrocortisone may improve
90-day survival in patients with septic shock.

20. • A single-center, randomized trial
demonstrated significant reduction in
vasopressor requirements and higher rates of
shock reversal with low-dose hydrocortisone
in patients with sepsis and cirrhosis.However,
hydrocortisone did not reduce mortality and
was associated with increase in shock
recurrence and gastrointestinal bleeding.
Arabi YM 2010

21. Antibiotics
• Diagnosis of sepsis in cirrhosis can be
challenging and requires a high index of
suspicion. This often leads to a delay in
initiation of empiric antibiotics, which, in turn,
is associated with worse outcomes. Therefore,
not only the choice of antibiotics, but the
timing of administration is important.
• Each hour delay in antimicrobial therapy
increases mortality by 1.86 times.

22. • Factors such as the source of infection,
community or hospital acquired, recent antibiotic
use, or history of colonization/infection by
multiresistant organisms should be considered
when choosing antibiotic coverage
• Patients without clinical improvement within 48-
72 hours on broad-spectrum antibiotics should
be considered for empiric antifungal therapy

23. ANTIBIOTICS CHART

24. • Procalcitonin levels have been studied as a
bacterial infection biomarker and as a tool to
guide antibiotic therapy. It has been proposed
that in stable critically ill patients,
procalcitonin levels of

25. SUPPORTIVE CARES